Lipopolysaccharide is a major constituent of the outer membranes of Gram negative bacteria. Studies have shown that it has the following three structural regions: 1) the 0-specific polysaccharide; 2) the common core region; and 3) a lipid component called lipid A. LPS is known to trigger many pathophysiological events in mammals, either when it is injected or when it accumulates due to Gram-negative infection. The lipopolysaccharide (LPS) from Escherichia coli is known to stimulate the immune system of animals, but it is relatively toxic.
In general, the hydrophobic lipid A moiety of the LPS is believed to be responsible for the pathophysiological effects of LPS, which also include B-lymphocyte mitogenesis, macrophage activation, interferon production, tumor regression, peripheral vascular collapse ("endotoxic" shock), pulmonary hypertension, pulmonary edema, disseminated intravascular coagulopathy and pyrogenicity.
It is also known that a monosaccharide precursor lipid X has some activity in stimulating 70Z/3 cells and that a large excess of lipid X will compete with lipid A, partially blocking its toxic effects.sup.13. It is also known that monophosphoryl lipid A from E. coli has numerous biological activities associated with LPS, but its toxicity is attenuated.sup.25. On the other hand, diacyldiphosphoryl lipid A from E. coli is known to have very low or no biological activities associated with LPS and it has moderate antagonistic activity against the activation of 70Z/3 cells by LPS (Kirkland and Takayama, unpublished data). It also is known that diphosphoryl lipid A from E. coli and Salmonella strains are highly toxic.sup.25.
The LPS obtained from Rhodopsuedomonas sphaeroides ATCC 17023 grown at 30.degree. C. was reported to be non-toxic by Strittmatter et. al..sup.21. The complete structure of the LPS from this source has now been established.sup.14,18,19. The structure of the lipid A moiety of the LPS from R. sphaeroides is strikingly similar to the lipid A of the toxic enterobacterial and Salmonella LPS.sup.9,22. The four major differences noted are the presence of a 3-ketotetradecanoate instead of a 3-hydroxytetradecanoate at the 2-position (R4), a .DELTA..sup.7 -tetradecanoate instead of a tetradecanoate in acyloxyacyl linkage at the 2'-position (R.sub.2), the presence of five fatty acids instead of six, and the presence of 3-hydroxydecanoate at the 3-position (R.sub.3) instead of 3-hydroxytetradecanoate of the glucosamine disaccharide of the R. sphaeroides lipid A. See Formula II for the diphosphoryl lipid A (DPLA) from R. sphaeroides.
Another nontoxic LPS from Rhodopsuedomonas capsulata ATCC 23782 was reported by Omar et al.sup.27. The lipid A from the LPS of this source has been prepared and its complete structure determined. This lipid A has 3-ketotetradecanoate at both 2- and 2'-positions (R.sub.2 and R.sub.4) of the glucosamine disaccharide, a.3-hydroxytetradecanoate at the 3'-position (R3), and .DELTA..sup.9 -dodecanoyloxydecanoate at the 3'-position (R.sub.1) (See Formula III for the structure of the DPLA from R. capsulata.)
There is a need for a safe and effective method of stimulating the immune systems of animals.